2022
Integrin Conformational Dynamics and Mechanotransduction
Kolasangiani R, Bidone T, Schwartz M. Integrin Conformational Dynamics and Mechanotransduction. Cells 2022, 11: 3584. PMID: 36429013, PMCID: PMC9688440, DOI: 10.3390/cells11223584.Peer-Reviewed Original ResearchConceptsCell-cell adhesionCell-extracellular matrixExtracellular ligandsIntegrin affinityConformational dynamicsIntegrin familyConformational statesConformational transitionTissue integrityCell functionCentral mediatorRemarkable convergenceMechanical forcesForce transmissionCytoskeletonMechanotransductionAdhesionFirm adhesionUnanswered questionsIntegrinsNew informationPathwayLigands
2021
Integrin-based mechanosensing through conformational deformation
Driscoll TP, Bidone TC, Ahn SJ, Yu A, Groisman A, Voth GA, Schwartz MA. Integrin-based mechanosensing through conformational deformation. Biophysical Journal 2021, 120: 4349-4359. PMID: 34509509, PMCID: PMC8553792, DOI: 10.1016/j.bpj.2021.09.010.Peer-Reviewed Original ResearchMeSH KeywordsCell AdhesionIntegrin alphaVbeta3IntegrinsLigandsMechanical PhenomenaProtein BindingTalinConceptsCellular mechanosensingFocal adhesion kinase activationIntegrin conformational activationLarge-scale conformational transitionsWild-type integrinIntegrin mutantsEmbryonic developmentConformational activationCellular stiffnessHigh-affinity stateKinase activationSubstrate stiffnessBiological processesIntegrin activationCell spreadingMutantsIntegrin conformationTraction stressConformational deformationConformational transitionIntegrinsMechanosensingSoluble ligandsAffinity stateMolecular-level information
2018
Vinculin and the mechanical response of adherent fibroblasts to matrix deformation
Rosowski KA, Boltyanskiy R, Xiang Y, Van den Dries K, Schwartz MA, Dufresne ER. Vinculin and the mechanical response of adherent fibroblasts to matrix deformation. Scientific Reports 2018, 8: 17967. PMID: 30568231, PMCID: PMC6299284, DOI: 10.1038/s41598-018-36272-9.Peer-Reviewed Original ResearchConceptsFocal adhesion protein vinculinAdhesion protein vinculinExtracellular matrix stiffnessIntegrin-mediated adhesionTraction forceProtein vinculinMechanical cuesCellular forcesMatrix stiffnessAdherent fibroblastsECM deformationMouse fibroblastsTraction stressMatrix deformationMechanical responseVinculinMechanical energyApparent stiffnessDeformationFibroblastsStiffnessCellsStretchForceExpression
2016
Force regulated conformational change of integrin αVβ3
Chen Y, Lee H, Tong H, Schwartz M, Zhu C. Force regulated conformational change of integrin αVβ3. Matrix Biology 2016, 60: 70-85. PMID: 27423389, PMCID: PMC5237428, DOI: 10.1016/j.matbio.2016.07.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomechanical PhenomenaBiotinylationCell AdhesionCell LineEndothelial CellsErythrocytesExtracellular MatrixFibronectinsGene ExpressionGlassHumansIntegrin alphaVbeta3KineticsLungMiceMolecular ProbesPoint MutationProtein BindingProtein ConformationSignal TransductionSingle Molecule ImagingConceptsConformational changesTransduce signalsSingle-molecule levelIntegrin functionBiomembrane force probeMolecular machinesPhysiological functionsCell adhesionCell surfaceExtracellular matrixPoint mutationsConformational transitionIntegrinsEssential roleTumor metastasisExtended conformationConformationDynamic equilibriumEctodomainMutationsForce probePhagocytosisMembraneAngiogenesisFunctionRal-Arf6 crosstalk regulates Ral dependent exocyst trafficking and anchorage independent growth signalling
Pawar A, Meier JA, Dasgupta A, Diwanji N, Deshpande N, Saxena K, Buwa N, Inchanalkar S, Schwartz MA, Balasubramanian N. Ral-Arf6 crosstalk regulates Ral dependent exocyst trafficking and anchorage independent growth signalling. Cellular Signalling 2016, 28: 1225-1236. PMID: 27269287, PMCID: PMC4973806, DOI: 10.1016/j.cellsig.2016.05.023.Peer-Reviewed Original ResearchMeSH KeywordsADP-Ribosylation Factor 6ADP-Ribosylation FactorsAnimalsCell AdhesionCell Line, TumorCell ProliferationCell Transformation, NeoplasticEmbryo, MammalianExocytosisExtracellular Signal-Regulated MAP KinasesFibroblastsHumansMembrane MicrodomainsMiceProtein TransportRal GTP-Binding ProteinsSignal TransductionConceptsARF6 activationRegulatory crosstalkActive RalIntegrin-dependent regulationOncogenic H-RasIndependent growthIntegrin-dependent activationAdhesion-dependent pathwayKey downstream mediatorSmall GTPase RalActive RalABladder cancer T24 cellsDependent traffickingRal functionIsoforms functionRaft microdomainsOncogenic RasPlasma membraneDependent regulationH-RasArf6Dependent activationDependent pathwayDownstream mediatorVital mediators
2015
Rac1 functions as a reversible tension modulator to stabilize VE-cadherin trans-interaction
Daneshjou N, Sieracki N, van Nieuw Amerongen GP, Conway D, Schwartz M, Komarova Y, Malik A. Rac1 functions as a reversible tension modulator to stabilize VE-cadherin trans-interaction. Journal Of Cell Biology 2015, 208: 23-32. PMID: 25559184, PMCID: PMC4284224, DOI: 10.1083/jcb.201409108.Peer-Reviewed Original ResearchActomyosinAdherens JunctionsAntigens, CDCadherinsCell AdhesionCells, CulturedEndothelial CellsEnzyme ActivationHumansKineticsMicroscopy, FluorescenceMicroscopy, VideoModels, BiologicalMyosin Type IIProtein BindingProtein Kinase InhibitorsProtein MultimerizationProtein StabilityRac1 GTP-Binding ProteinRho-Associated KinasesTime-Lapse ImagingTransfection
2014
Integrin adjunct therapy for melanoma
Andarawewa KL, Moissoglu K, Lee C, Ando Y, Yu M, Debnath P, Shannon JD, Sirinivasan S, Conaway MR, Weber MJ, Schwartz MA. Integrin adjunct therapy for melanoma. Pigment Cell & Melanoma Research 2014, 28: 114-116. PMID: 25264294, PMCID: PMC6542633, DOI: 10.1111/pcmr.12320.Peer-Reviewed Original Research
2013
Integrins in mechanotransduction
Ross TD, Coon BG, Yun S, Baeyens N, Tanaka K, Ouyang M, Schwartz MA. Integrins in mechanotransduction. Current Opinion In Cell Biology 2013, 25: 613-618. PMID: 23797029, PMCID: PMC3757118, DOI: 10.1016/j.ceb.2013.05.006.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAnimalsCell AdhesionExtracellular MatrixHumansIntegrinsMechanotransduction, CellularConceptsMolecular mechanismsIntegrin-mediated adhesionImportant regulatory eventActin cytoskeletonRegulatory eventsExtracellular matrixNormal physiologyCell functionMajor insightsCentral roleCellsRecent advancesCytoskeletonEffect of forceMechanotransductionAdhesionIntegrinsPathwayPhysiologyMechanismRecent work
2011
Effects of integrin-mediated cell adhesion on plasma membrane lipid raft components and signaling
Norambuena A, Schwartz MA. Effects of integrin-mediated cell adhesion on plasma membrane lipid raft components and signaling. Molecular Biology Of The Cell 2011, 22: 3456-3464. PMID: 21795400, PMCID: PMC3172269, DOI: 10.1091/mbc.e11-04-0361.Peer-Reviewed Original ResearchConceptsLipid raft componentsRaft componentsLipid raftsCyclic adenosine monophosphateCell detachmentCell adhesionLipid raft markersGlycosylphosphatidylinositol-linked proteinsRaft associationRaft markersRho GTPasesNonraft fractionsDetachment of cellsElevation of cAMPStudy of integrinsTermination of growthPlasma membraneH-RasAnchorage dependenceKey defenseCell growthFlotillin2Sucrose gradientsCancer metastasisLipid tailsSuper-Resolution Microscopy: A New Dimension in Focal Adhesions
Schwartz MA. Super-Resolution Microscopy: A New Dimension in Focal Adhesions. Current Biology 2011, 21: r115-r116. PMID: 21300274, DOI: 10.1016/j.cub.2010.12.025.Peer-Reviewed Original Research
2010
Cell adhesion: integrating cytoskeletal dynamics and cellular tension
Parsons JT, Horwitz AR, Schwartz MA. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nature Reviews Molecular Cell Biology 2010, 11: 633-643. PMID: 20729930, PMCID: PMC2992881, DOI: 10.1038/nrm2957.Peer-Reviewed Original ResearchConceptsRho GTPasesGuanine nucleotide exchange factorsNucleotide exchange factorsGTPase-activating proteinsMyosin II activityActin-myosin contractionCytoskeletal dynamicsActin cytoskeletonCellular tensionExchange factorRho proteinsProtein TyrAdhesion dynamicsMorphogenetic processesCell rearAdhesion sizeCell frontIntegrin clusteringActin polymerizationRho activationMyosin IIDownstream signalingFeedback loopCell migrationComplex feedback loopsMyosin II directly binds and inhibits Dbl family guanine nucleotide exchange factors: a possible link to Rho family GTPases
Lee CS, Choi CK, Shin EY, Schwartz MA, Kim EG. Myosin II directly binds and inhibits Dbl family guanine nucleotide exchange factors: a possible link to Rho family GTPases. Journal Of Cell Biology 2010, 190: 663-674. PMID: 20713598, PMCID: PMC2928003, DOI: 10.1083/jcb.201003057.Peer-Reviewed Original ResearchMeSH KeywordsActomyosinAnimalsBinding SitesCdc42 GTP-Binding ProteinCell AdhesionCell MovementEnzyme ActivationGuanine Nucleotide Exchange FactorsHumansJurkat CellsMiceMyosin Type IINIH 3T3 CellsPlatelet-Derived Growth FactorProtein BindingRac1 GTP-Binding ProteinRatsRecombinant Fusion ProteinsRho GTP-Binding ProteinsRho Guanine Nucleotide Exchange FactorsRNA, Small InterferingConceptsFocal complex formationDbl family guanineMyosin IIExchange factorFamily guanineATPase activityNonmuscle myosin IIComplex formationGEF activitySpatiotemporal regulationRho familyCdc42 GTPasesAdhesion dynamicsRho GTPasesCdc42 activationLamellipodial protrusionCell protrusionsActomyosin contractionGEFNIH3T3 fibroblastsFunctional linkCell migrationGTPasesCatalytic siteHomology modulesSpatiotemporal organization, regulation, and functions of tractions during neutrophil chemotaxis
Shin ME, He Y, Li D, Na S, Chowdhury F, Poh YC, Collin O, Su P, de Lanerolle P, Schwartz MA, Wang N, Wang F. Spatiotemporal organization, regulation, and functions of tractions during neutrophil chemotaxis. Blood 2010, 116: 3297-3310. PMID: 20616216, PMCID: PMC2995358, DOI: 10.1182/blood-2009-12-260851.Peer-Reviewed Original Research
2009
RalA-Exocyst Complex Regulates Integrin-Dependent Membrane Raft Exocytosis and Growth Signaling
Balasubramanian N, Meier JA, Scott DW, Norambuena A, White MA, Schwartz MA. RalA-Exocyst Complex Regulates Integrin-Dependent Membrane Raft Exocytosis and Growth Signaling. Current Biology 2009, 20: 75-79. PMID: 20005108, PMCID: PMC2822103, DOI: 10.1016/j.cub.2009.11.016.Peer-Reviewed Original ResearchConceptsPlasma membraneRecycling endosomesGrowth signalingActivation of Arf6Small GTPase RalACaveolin-dependent internalizationLipid raft microdomainsAnchorage-independent growthEffects of integrinsExocyst complexActive RalARaft microdomainsMembrane raftsRaft markersIntegrin signalingPancreatic cancer cellsRalAAnchorage dependenceAnchorage independenceCell growthSignalingCell detachmentCancer cellsEndosomesExocytosisRho GDP Dissociation Inhibitor 2 Suppresses Metastasis via Unconventional Regulation of RhoGTPases
Moissoglu K, McRoberts KS, Meier JA, Theodorescu D, Schwartz MA. Rho GDP Dissociation Inhibitor 2 Suppresses Metastasis via Unconventional Regulation of RhoGTPases. Cancer Research 2009, 69: 2838-2844. PMID: 19276387, PMCID: PMC2701105, DOI: 10.1158/0008-5472.can-08-1397.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCdc42 GTP-Binding ProteinCell AdhesionGuanine Nucleotide Dissociation InhibitorsHumansLung NeoplasmsMiceRac1 GTP-Binding ProteinRho GTP-Binding ProteinsRho Guanine Nucleotide Dissociation Inhibitor betaRho-Specific Guanine Nucleotide Dissociation InhibitorsRhoA GTP-Binding ProteinTumor Suppressor ProteinsUrinary Bladder NeoplasmsVinculinConceptsRho GTPasesFamily of proteinsGDP dissociation inhibitor 2Rho GDP dissociation inhibitor 2Dissociation inhibitor 2Membrane targetingMembrane associationPoint mutantsMetastasis suppressorRac1 activityGTPasesMetastasis suppressionInhibitor 2Suppress metastasisRhoGDI2ProteinSuppression correlatesRhoGDI1Weak inhibitorInhibitionRhoGTPasesMutantsMetastasis inhibitionStrong inhibitionSuppressorCadherin Adhesion, Tissue Tension, and Noncanonical Wnt Signaling Regulate Fibronectin Matrix Organization
Dzamba BJ, Jakab KR, Marsden M, Schwartz MA, DeSimone DW. Cadherin Adhesion, Tissue Tension, and Noncanonical Wnt Signaling Regulate Fibronectin Matrix Organization. Developmental Cell 2009, 16: 421-432. PMID: 19289087, PMCID: PMC2682918, DOI: 10.1016/j.devcel.2009.01.008.Peer-Reviewed Original ResearchConceptsCadherin adhesionBlastocoel roofPlanar cell polarity signalingMatrix assemblyCell polarity signalingCell-cell adhesionFN fibril formationFN fibril assemblyPolarity signalingFocal adhesionsActin reorganizationXenopus embryosRegulatory pathwaysMyosin contractilityFibronectin matrixMatrix organizationSpatiotemporal localizationCultured cellsCell surfaceAnalogous roleFibril formationFibril assemblyFibrillar matrixMechanical tensionAssemblyThe Force Is with Us
Schwartz MA. The Force Is with Us. Science 2009, 323: 588-589. PMID: 19179515, DOI: 10.1126/science.1169414.Peer-Reviewed Original Research
2008
Cell adhesion receptors in mechanotransduction
Schwartz MA, DeSimone DW. Cell adhesion receptors in mechanotransduction. Current Opinion In Cell Biology 2008, 20: 551-556. PMID: 18583124, PMCID: PMC2581799, DOI: 10.1016/j.ceb.2008.05.005.Peer-Reviewed Original ResearchConceptsAdhesion receptorsCell fate decisionsCadherin-mediated adhesionCell adhesion receptorsFate decisionsMorphogenetic movementsTissue-level responsesCultured cellsExtracellular matrixMechanotransductionLevel responseCellsCytoskeletonCadherinReceptorsOrganismsAdhesionIntegrinsPathwayMechanical stimulationIntracellularMechanismMechanical stressResponseCentral mechanismsEndogenous RhoG is dispensable for integrin-mediated cell spreading but contributes to Rac-independent migration
Meller J, Vidali L, Schwartz MA. Endogenous RhoG is dispensable for integrin-mediated cell spreading but contributes to Rac-independent migration. Journal Of Cell Science 2008, 121: 1981-1989. PMID: 18505794, PMCID: PMC2759683, DOI: 10.1242/jcs.025130.Peer-Reviewed Original Research
2007
Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts
Balasubramanian N, Scott DW, Castle JD, Casanova JE, Schwartz MA. Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts. Nature Cell Biology 2007, 9: 1381-1391. PMID: 18026091, PMCID: PMC2715295, DOI: 10.1038/ncb1657.Peer-Reviewed Original ResearchConceptsPlasma membraneLipid raftsAnchorage-dependent signalingArf6-dependent mannerCaveolin-dependent internalizationSmall GTPase Arf6Microtubule-dependent traffickingIntegrin-mediated adhesionRecycling endosomesGTPase Arf6Membrane raftsDetachment of cellsCell spreadingF-actinRaftsArf6MicrotubulesEndosomesRac1TraffickingMembraneCellsEndocytosisSignalingPathway